6-Bromopyrazine-2-carboxamide - ≥97% , CAS No.1209459-76-6

CAS: 1209459-76-6 Cat. No.: B1012848 PubChem CID: 17768039

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥97%

Nomi e identificatori

Sorrisi canonici

C1=C(N=C(C=N1)Br)C(=O)N

IUPAC Name

6-bromopyrazine-2-carboxamide

InChIKey

PVULJUJAGMJHRA-UHFFFAOYSA-N

INCHI

1S/C5H4BrN3O/c6-4-2-8-1-3(9-4)5(7)10/h1-2H,(H2,7,10)

Isomeri SMILES

C1=C(N=C(C=N1)Br)C(=O)N

PubChem CID

17768039

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Diazines
      • Subclass Pyrazines
        • Level5 Pyrazine carboxylic acids and derivatives
          • Level6 Pyrazinecarboxamides

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Diazines
• Subclass: Pyrazines
• Intermediate Tree Nodes: Pyrazine carboxylic acids and derivatives
• Direct Parent: Pyrazinecarboxamides
• Alternative Parents: 2-heteroaryl carboxamides Aryl bromides Heteroaromatic compounds Primary carboxylic acid amides Azacyclic compounds Organooxygen compounds Organonitrogen compounds Organobromides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Pyrazinecarboxamide - 2-heteroaryl carboxamide - Aryl bromide - Aryl halide - Heteroaromatic compound - Carboxamide group - Primary carboxylic acid amide - Carboxylic acid derivative - Azacycle - Organooxygen compound - Organonitrogen compound - Organobromide - Organohalogen compound - Organic oxide - Organic oxygen compound - Hydrocarbon derivative - Organic nitrogen compound - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as pyrazinecarboxamides. These are compounds containing a pyrazine ring which bears a carboxamide.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Proprietà chimiche e fisiche

• Peso molecolare: 202.010 g/mol
• XLogP3: 0.300
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 200.954 Da
• Monoisotopic Mass: 200.954 Da
• Topological Polar Surface Area: 68.900 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 141.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

No vendor-validated biological assay protocols or analytical application methods are specified for this item.

• General guidance (informational):
  • Compound preparation for screening: Dissolve in dry DMSO to make a 10–100 mM stock; vortex and sonicate if needed; filter through 0.2 µm PTFE; store aliquots at −20 C for long-term use to minimize freeze–thaw.
  • Analytical characterization: Confirm identity/purity by 1H/13C NMR (DMSO‑d6 or CD3OD), HRMS (ESI), and HPLC/UPLC. The Br atom gives a characteristic M/M+2 (≈1:1) isotopic pattern in MS.
  • Reaction setup: For cross-coupling, pre-dry under high vacuum (e.g., 40–60 C) and use anhydrous, degassed solvents. Charge substrate as a DMF/DMSO solution if solid handling is limiting.

For any specific, validated protocols, please refer to peer-reviewed literature or develop method-specific SOPs appropriate to your laboratory.

Biological Roles

• Item-specific biological/biochemical data: Not specified for this item; refer to primary literature where applicable. For research use only.

• General/literature context for the scaffold:

  • Pyrazine-2-carboxamide motifs appear in diverse small-molecule libraries due to their dual H-bonding capability and electron-deficient aromatic core, which can engage in π-stacking and polar interactions within protein binding sites.
  • The diazine ring reduces basicity compared to pyridines, often yielding neutral, polar molecules suitable for fragment-based screening.
  • The C6 position enables rapid SAR diversification via cross-coupling or SNAr to probe hydrophobic pockets or modulate electronics.
  • The primary carboxamide can form intramolecular H-bonds or be N-alkylated/acylated to tune solubility and permeability.

• ADME-relevant features (general):

  • Amides typically reduce membrane permeability relative to corresponding nitriles/esters but can enhance metabolic stability and aqueous compatibility.
  • Bromine substitution modulates lipophilicity and may serve as a handle for late-stage diversification rather than a final feature.

No claims are made regarding any biological activity of this specific item. Any biological testing should be performed under appropriate approvals, with proper controls and in accordance with institutional guidelines.

Buffer Applications

This compound is not a buffering reagent and is not typically employed to prepare biological or analytical buffer systems.

• If dissolution in buffers is needed for assays, prepare concentrated DMSO stocks and dilute into the desired buffer, keeping final DMSO content low (≤1–2%) to minimize precipitation.
• For pH-sensitive studies, note that primary amides are generally neutral across physiological pH; pH adjustment will not significantly ionize the molecule.

For dedicated buffer preparation, consider standard buffering agents (e.g., phosphate, HEPES, MOPS) appropriate to your pH range.

Green Alternatives

While the substrate itself is a brominated heteroarene, greener choices can be made around solvents, bases, and coupling partners.

• Greener solvent options (literature/general):

  • Replace dioxane/DMF with 2-MeTHF, CPME, or propylene carbonate where compatible.
  • Use aqueous micellar media (e.g., TPGS-750-M) for Suzuki couplings to reduce organic solvent usage.
  • Prefer ethanol or water/ethanol mixtures for SNAr when feasible.

• Base and reagent choices:

  • Use inorganic carbonates/phosphates (K2CO3, K3PO4) over strong alkoxides to improve safety and waste profiles.
  • Select boronic acids/esters over stannanes (to avoid organotin waste) for C–C formation.

• Energy and process intensification:

  • Employ flow chemistry or microwave heating to shorten reaction times and reduce energy consumption.
  • Room-temperature couplings using modern catalysts (e.g., Pd–NHC systems) can cut heating demand.

• Comparative snapshot (general; not item-specific specifications):

  • Traditional: DMF/dioxane, high temperatures (80–120 C), strong bases; effective but higher EHS burden.
  • Greener: 2-MeTHF/H2O or ethanol/H2O with Pd catalysts at 40–80 C; improved safety and renewability.

Trade-offs: Greener solvents may change solubility and rate; heterogeneous conditions can require higher catalyst loadings. Validate on small scale and quantify PMI/E-factor to guide selection.

Pharmaceutical Uses

• Item-specific pharmacopeial/excipient status: Not specified for this item; refer to CoA/Spec Sheet. This material is provided strictly for research use only.

• General role in pharmaceutical R&D (no therapeutic claims):

  • Serves as a heteroaryl building block/intermediate in medicinal chemistry campaigns, enabling rapid preparation of analog libraries through C–C and C–N cross-couplings at the 6-position.
  • The pyrazine-2-carboxamide core provides a polar, hydrogen-bonding motif favored in fragment-based lead discovery and structure-enabled design.
  • The aryl bromide can act as a synthetic handle for installing radiolabels (via halogen exchange) or for late-stage diversification to optimize DMPK properties.

• Developability considerations (general):

  • Solid-state form and polymorphism can influence processability; verify with PXRD/DSC if scaling.
  • Residual Pd/Ni from couplings should be controlled per ICH Q3D when transitioning to GMP contexts (not applicable to research-only supply, but relevant to route scouting).
  • Solubility enhancement strategies (salt formation is not applicable to neutral amides; consider prodrugs, co-crystals, or formulation with solubilizing excipients) may be explored for related scaffolds.

Physical Properties

• Item-specific specifications: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general expectations for 6-bromopyrazine-2-carboxamide (informational only; not product specifications):

  • Physical state: Typically an off-white to light tan crystalline solid (heteroaryl carboxamides are commonly solids).
  • Molecular formula: C5H4BrN3O (literature)
  • Molecular weight: ~202.01 g/mol (literature)
  • Polarity: Moderately polar due to the carboxamide and diazine nitrogens; contains one heavy halogen.
  • Hydrogen bonding: One H-bond donor (–NH2), multiple acceptors (amide C=O; ring nitrogens).
  • Expected solubility profile: Good solubility in polar aprotic solvents (DMSO, DMF, NMP). Often sparingly soluble to moderately soluble in alcohols; low solubility in nonpolar hydrocarbons and water. Actual solubility can vary with batch and polymorph.
  • Partitioning: Likely low to moderate logP due to amide and ring nitrogens; exact logP/pKa not established here.

• Optical/refractive data: Not specified for this item; refer to CoA/Spec Sheet.

• Thermal data (mp/bp, decomposition): Not specified for this item; refer to CoA/Spec Sheet.

Note: The above literature descriptors are provided to aid planning of handling and solvent selection. For validated numeric values relevant to your lot, please consult the CoA/Spec Sheet.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

• How to interpret grade when provided (general guidance):

  • Research/Biochemical grade typically emphasizes low inorganic/organic residues and suitability for discovery chemistry and biochemical screening.
  • HPLC grade (if applicable to solvents) relates to low UV absorbance/particulate—less relevant to a solid building block, but residual solvent content and chromatographic purity are still key.
  • Assay/purity reporting for heteroaryl building blocks is often by HPLC/UPLC with UV detection and sometimes 1H NMR. Trace halides, residual metals (Pd, Ni, Cu), and water content may be reported when relevant to coupling chemistry.

• Stabilizers/inhibitors: None indicated for this item. If stabilizers or salt forms are used in a related product, they will be stated explicitly on the CoA/label.

• What to check on receipt:

  • Appearance vs. CoA, assay method and purity, residual solvent profile, water content (e.g., KF) if sensitive applications require it, and residual metals for catalytic processes.
  • If your application is moisture- or base-sensitive, consider re-drying under vacuum and verifying by KF before use.

For lot-specific specifications (assay, melting point, residual metals, water), please consult the CoA/Spec Sheet.

Reaction and Applications

6-Bromopyrazine-2-carboxamide is a versatile heteroaryl building block that combines an electron-poor diazine ring with an aryl bromide and a directing/coordination-capable carboxamide.

• Cross-coupling platform (literature/general):

  • Suzuki–Miyaura: Install aryl/heteroaryl/alkenyl groups at C6 using Pd catalysts (e.g., Pd(dppf)Cl2, Pd2(dba)3 + SPhos) with bases such as K2CO3, Cs2CO3, or K3PO4 in dioxane/H2O, toluene/H2O, or 2-MeTHF/H2O.
  • Buchwald–Hartwig amination: Convert C6–Br to C6–NR2 using Pd/XPhos/BrettPhos ligands; strong bases (NaOtBu) in toluene/dioxane/THF. The electron-poor pyrazine typically couples efficiently.
  • Negishi/Stille/Kumada: Viable for alkenyl/alkyl or stannyl partners when specific functionality tolerance is needed.

• Nucleophilic aromatic substitution (SNAr): The diazine core activates the ring toward SNAr. Although bromide is a poorer SNAr leaving group than fluoride, strong conditions (e.g., NaOMe/MeOH, amines in DMSO, elevated temperature) can enable substitution, especially with additional activation from the amide.

• Directed metalation/minor pathways:

  • Amide coordination can assist site-selectivity in metal-catalyzed C–H functionalization on related scaffolds; practitioners can explore orthogonal diversification at C3/C5 using Pd/Cu catalysis.

• Medicinal chemistry context (general): Pyrazine-2-carboxamide motifs participate in H-bonding networks and enhance polarity; C6 diversification supports SAR exploration across halogen, aryl, amine, and alkyl handles.

• Practical notes:

  • Maintain anhydrous/inert conditions for organometallic couplings; pre-dry the solid if necessary.
  • Heteroaryl bromides can be prone to debromination; optimize ligand choice and base to minimize side reactions.
  • Monitor by UPLC–MS; the diazine absorbs in UV (250–320 nm).

Reaction Conditions

General literature guidance for transforming 6-bromopyrazine-2-carboxamide (informational only; optimize per system):

• Suzuki–Miyaura coupling (C6 arylation/alkenylation):

  • Catalyst: 1–3 mol% Pd(dppf)Cl2·DCM or Pd2(dba)3 (1 mol% Pd) + SPhos (2–3 mol%).
  • Base: K3PO4 (2–3 equiv) or K2CO3/Cs2CO3.
  • Solvent: 1,4-dioxane/H2O (3:1), toluene/H2O, or 2-MeTHF/H2O.
  • Temperature/Time: 60–90 C, 2–12 h.

• Buchwald–Hartwig amination (C6 amination):

  • Catalyst: Pd2(dba)3 (1 mol% Pd) + BrettPhos or XPhos (2–4 mol%); or Pd-PEPPSI-type NHC catalysts.
  • Base: NaOtBu or K3PO4 (2–3 equiv).
  • Solvent: Toluene, dioxane, or tAmOH; 2-MeTHF as greener option.
  • Temperature/Time: 70–110 C, 4–16 h.

• SNAr (nucleophilic substitution of Br under forcing conditions):

  • Nucleophile: Alkoxides or amines (e.g., NaOMe/MeOH; primary amines in DMSO).
  • Conditions: 80–140 C (sealed tube), hours to overnight. Fluoride leaving groups are superior; bromide requires stronger conditions.

• Sonogashira alkynylation (if pursued):

  • Catalyst: 1–3 mol% Pd(PPh3)2Cl2 + 5–10 mol% CuI.
  • Base/Solvent: Et3N or iPr2NH in THF/DMF.
  • Temperature: RT to 60 C.

• Workup/analysis tips:

  • Quench with aqueous NH4Cl; extract with EtOAc; charcoal treat to remove Pd.
  • Monitor by UPLC–MS; expect M and M+2 isotopic pattern due to Br.

These are starting points; substrate, partner, and scale will dictate optimization.

Safety and Handling

• Item-specific GHS/SDS data:

  • Signal Word: Not specified for this item; refer to SDS.
  • Hazard Statements (H-Statements): Not specified for this item; refer to SDS.
  • GHS Classification and Pictograms: Not specified for this item; refer to SDS.

• General safety considerations for heteroaryl bromides and carboxamides (informational; not a substitute for SDS):

  • Avoid inhalation of dust and contact with skin/eyes. Use in a fume hood to minimize exposure.
  • Wear appropriate PPE: lab coat, gloves (e.g., nitrile), and splash goggles. Consider double-gloving for extended operations in DMF/DMSO solutions.
  • Handling: Minimize dust generation. Use antistatic measures when weighing dry powders. Avoid strong oxidizers and strong bases that may induce hydrolysis of the amide under forcing conditions.
  • Incompatibilities: Strong reducing metals in polar aprotic solvents (for coupling conditions) should be handled under inert atmosphere. Avoid prolonged contact with strong acids/bases if amide hydrolysis or ring opening is a concern.
  • First aid (overview): If on skin/eyes, rinse with water for ≥15 minutes and remove contaminated clothing/contact lenses. If inhaled, move to fresh air. If ingested, rinse mouth and seek medical attention. Always follow your institution’s emergency procedures.
  • Fire safety: Solid is combustible; use CO2, dry chemical, or foam. Brominated aromatics may produce HBr and NOx upon thermal decomposition—firefighters should use self-contained breathing apparatus.

Always consult the official SDS for authoritative hazard classifications, exposure limits, and spill/accidental release procedures. For research use only.

Solvent Selection

This compound is a polar, heteroaryl carboxamide with an aryl bromide. Solvent choice should balance dissolution, stability, and compatibility with the intended transformation.

• Item-specific solubility data: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general guidance:

  • Highly suitable: DMSO, DMF, NMP—good solvating power for heteroaryl amides; excellent for stock solutions and coupling reactions.
  • Moderately suitable: Acetonitrile, ethanol, methanol, isopropanol—may dissolve at elevated temperature or lower concentrations.
  • Poor solvents: Alkanes, MTBE, hexanes; typically very low solubility.
  • Aqueous media: Expect low aqueous solubility; co-solvents or pH adjustments have limited effect due to non-ionizable amide (under neutral conditions).

• Selection by application:

  • Cross-coupling (Suzuki/Negishi/Stille): Use polar aprotic media (dioxane, THF, 2-MeTHF, CPME, toluene) often mixed with water or alcohols; substrate can be charged as a concentrated solution in DMF/DMSO for dosing.
  • SNAr or metalation: DMF/DMSO/NMP advantageous for polar transition states; ensure anhydrous conditions.
  • Biological screening: Prepare concentrated DMSO stock (e.g., 10–100 mM) and dilute into assay buffers with ≤1–2% final DMSO to mitigate precipitation.

• Practical tips:

  • Warm gently (40–60 C) and sonicate to aid dissolution.
  • Filter through 0.2 µm PTFE before sensitive uses.
  • Verify chemical stability in chosen solvent over time; amides are generally stable, but monitor for hydrolysis under strong basic or high-temperature conditions.

Storage and Reconstitution

• Item-specific storage:

  • Storage Conditions: Room temperature (as provided). Store tightly closed in a dry, well-ventilated place, protected from light and moisture.
  • Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

• Stability considerations (general):

  • The amide and heteroaryl bromide are typically stable under ambient dry conditions. Avoid prolonged exposure to high humidity or strong light to prevent hydrolysis or discoloration.
  • For long-term archiving, many laboratories store heteroaryl building blocks desiccated and, optionally, under inert gas.

• Reconstitution/dissolution (general guidance):

  • Prepare concentrated stocks in anhydrous DMSO or DMF. Typical screening stocks: 10–100 mM.
  • To aid dissolution, warm gently (40–60 C) and sonicate; avoid excessive heating to preclude decomposition.
  • For aqueous assays, dilute DMSO stocks into buffer with thorough mixing; keep final DMSO ≤1–2% v/v to minimize precipitation.

• Freeze–thaw:

  • If preparing solutions for repeated use, aliquot to avoid multiple freeze–thaw cycles. Inspect for precipitation or degradation before use.

Always consult the CoA and SDS for lot-specific stability and handling recommendations. For research use only.

Structure and Identity

Summary: 6-Bromopyrazine-2-carboxamide is a halogenated diazine carboxamide useful as a heteroaryl building block.

• Item-specific (from Product Data):

  • SKU: B1012848
  • Product Name: 6-Bromopyrazine-2-carboxamide
  • CAS: 1209459-76-6
  • PubChem CID: 17768039
  • InChIKey: 288288 (as provided)
  • Storage Conditions: Room temperature
  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/Literature structure information (not item-specific):

  • Expected molecular formula (literature): C5H4BrN3O
  • Approximate molecular weight (literature): ~202.01 g/mol
  • Core scaffold: Pyrazine (1,4-diazine) ring bearing two ring nitrogens in para relationship.
  • Substitution pattern: Carboxamide (–C(=O)NH2) at the 2-position; bromine at the 6-position (para to each other across the ring).
  • Functional groups: Aryl bromide (for cross-coupling/SNAr), primary carboxamide (H-bond donor/acceptor), diazine heteroaromatic (π-accepting, electron-poor ring).
  • 2D description: A six-membered aromatic ring with N atoms at positions 1 and 4. At C2, a carbonyl carbon double-bonded to oxygen and single-bonded to an –NH2; at C6, a bromine substituent.

• Structure identifiers:

  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • InChI: Not specified for this item; refer to CoA/Spec Sheet.

Synthetic Utility

Key functional elements make 6-bromopyrazine-2-carboxamide a highly adaptable synthon:

• Aryl bromide at C6:

  • Cross-coupling gateway to C–C (Suzuki, Negishi, Stille, Sonogashira after bromide–iodide exchange or direct if alkyne partner tolerates) and C–N (Buchwald–Hartwig) bonds.
  • Facilitates installation of heteroaryl, alkenyl, alkyl, or amine substituents for SAR expansion.

• Pyrazine (1,4-diazine) ring:

  • Electron-deficient aromatic ring enhances reactivity toward nucleophilic aromatic substitution under appropriate conditions.
  • Coordinates to transition metals, which can influence regioselectivity in catalysis and enable directed C–H activation on neighboring positions in derivatives.

• Carboxamide at C2:

  • Acts as a hydrogen-bonding and polarity-tuning group; can be transformed to other functionalities (e.g., dehydration to nitrile, Hofmann/Curtius-type rearrangements on suitable derivatives, N-acylation/alkylation for amide diversification).
  • Serves as a weak directing group and potential ligand for metal-mediated transformations.

• Retrosynthetic value:

  • Forward diversification from a common core enables parallel synthesis: maintain the carboxamide constant while varying C6 substituents.
  • Alternatively, start from 6-substituted pyrazine-2-carboxylic acids and convert to amides after cross-coupling to manage functional group compatibility.

• Practical considerations:

  • Protect amide if strongly basic metalations are required.
  • Choose ligands that accommodate electron-poor heteroaryl bromides (e.g., BrettPhos, XPhos, RuPhos) and consider catalyst poisoning by ring nitrogens—use excess ligand or additives as needed.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, enzyme, or affinity reagent.

• No antigen/epitope, clone, isotype, or species reactivity data are relevant to this compound.
• For biochemical assays using this compound as a test article, define targets and specificity empirically in your experimental design.